1. Field of the Invention
This invention relates to the receptors for human Mob-5 (IL-24), and the detection of Mob-5 receptor expression and/or the presence of the Mob-5 receptor as potential markers for the early diagnosis of cancer. Methods for inhibiting the interaction between Mob-5 and the Mob-5 receptors are also provided.
2. Background Art
Mob-5 (IL-24), a gene constitutively activated by oncogenic Ras, encodes a secreted protein that exhibits significant homology to the IL-10 family of cytokines (See U.S. Application Ser. No. 60/178,185, which is herein incorporated by reference in its entirety). To provide insight into the biochemical and biological functions of Mob-5/Mda-7 in normal development as well as during cell transformation and tumorigenesis, the present invention provides the identification and characterization of its functional cell surface receptor. This invention shows that Mob-5 is normally expressed in activated PBMCs (peripherial blood mononuclear cells) and its expression is deregulated in cancer tissues. Namely, under normal circumstances, Mob-5 (IL-24) is secreted by T cells and binds to its receptors on target cells at the site of infection or injury to promote healing, which involves proliferation. This invention shows that, in cancer, activation of oncogenes such as ras and the loss of p53 tumor-suppressor genes lead to over expression of both Mob-5 and its receptors in the same cells. Thus, such autocrine loops allow cancer cells to stimulate themselves for unregulated cell proliferation. The present invention provides compositions and methods for inhibiting or blocking these autocrine loops, thus inhibiting cancer. Furthermore, the present invention provides the surprising discovery that Mob-5 binds to a Mob-5 receptor that consists of a new combination of two previously known class II cytokine receptor subunits, thus providing a strong molecular basis for cross-talk among the IL-10 family of cytokines.